Sodium hydride → HCID 66956553, compound

HRID 2066682Notes

Reaction equation

HRID 2066682 reaction equation
[N+:1]([C:4]1[N:5]=[C:6]2[N:11]([CH:12]=1)[CH2:10][CH:9]([CH2:13][OH:14])[CH2:8][O:7]2)([O-:3])=[O:2].[I:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH2:19]Br.[H-].[Na+]>CN(C=O)C>[I:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH2:19][O:14][CH2:13][CH:9]1[CH2:8][O:7][C:6]2=[N:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][N:11]2[CH2:10]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27593613-Iodobenzyl bromideHCID 66956639HCID 66956639, compound

Product 1

HCID 66956553HCID 66956553, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of oxazine alcohol 180 (see Example 2MMM) (200.3 mg, 1.01 mmol) and 3-iodobenzyl bromide (406 mg, 1.37 mmol) in anhydrous DMF (7.5 mL) under N2 at 0° C. was treated with 60% NaH (57 mg, 1.43 mmol), then quickly degassed and resealed under N2. After stirring at room temperature for 140 min, the mixture was cooled (CO2/acetone), quenched with ice/aqueous NaHCO3 (10 mL) and diluted with water (40 mL) to precipitate a crude solid, which was collected by filtration and washed with water and petroleum ether (0.49 g). The filtrate was extracted with EtOAc (3×80 mL), and then the extracts were washed with brine (50 mL). The combined extracts were evaporated to dryness and the residue was combined with the solid above and chromatographed on silica gel. Elution with 0-1% EtOAc/CH2Cl2 firstly gave foreruns, and then further elution with 1-2% EtOAc/CH2Cl2 gave 6-{[(3-iodobenzyl)oxy]methyl}-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (182) (184 mg, 44%) as a cream solid: mp (CH2Cl2/hexane) 127-130° C.; 1H NMR (CDCl3) δ 7.69-7.62 (m, 2H), 7.40 (s, 1H), 7.24 (m, 1H), 7.10 (br t, J=8.0 Hz, 1H), 4.51 (dd, J=11.4, 3.1 Hz, 1H), 4.48 (d, J=12.3 Hz, 1H), 4.44 (d, J=12.2 Hz, 1H), 4.35 (dd, J=11.4, 7.7 Hz, 1H), 4.14 (dd, J=12.3, 5.5 Hz, 1H), 4.02 (dd, J=12.3, 7.4 Hz, 1H), 3.60 (dd, J=9.6, 5.8 Hz, 1H), 3.54 (dd, J=9.6, 6.7 Hz, 1H), 2.66 (m, 1H). Anal. (C14H14IN3O4) C, H, N.

Workup

  1. customat 0° C.
  2. customquickly degassed
  3. temperaturethe mixture was cooled (CO2/acetone)
  4. customquenched with ice/aqueous NaHCO3 (10 mL)
  5. additiondiluted with water (40 mL)
  6. customto precipitate a crude solid, which
  7. filtrationwas collected by filtration
  8. washwashed with water and petroleum ether (0.49 g)
  9. extractionThe filtrate was extracted with EtOAc (3×80 mL)
  10. washthe extracts were washed with brine (50 mL)
  11. customThe combined extracts were evaporated to dryness
  12. customchromatographed on silica gel
  13. washElution with 0-1% EtOAc/CH2Cl2 firstly gave foreruns
  14. washfurther elution with 1-2% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-c17081b842e44853aeb8383c77798db3
Source dataset
uspto-grants-2012_10
Patent number
US08293734B2

Reaction notes

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